Immunostimulating coating for surgical devices

ABSTRACT

The present invention discloses an immunostimulating agent that may be applied to various surgical devices to promote rapid healing and the ready acceptance and integration of the surgical devices with the body tissues at the surgical site.

FIELD OF THE INVENTION

[0001] The present invention is drawn to a coating for surgical devicesthat facilitates the incorporation of a surgical device into the tissuesat a surgical site.

BACKGROUND OF THE INVENTION

[0002] It has become well known in the surgical arts to utilize variousorganic (autologous and homologous) and synthetic surgical devices at asurgical site to reinforce or augment the tissues being repaired orotherwise modified. These surgical devices include many distinctstructures, including but not limited to surgical meshes, plates,screws, sutures, heart valves, bulking compounds, breast implants, andreplacement joints. These devices may be fashioned from many differentorganic and inorganic materials.

[0003] While the functions of the aforementioned surgical devices arevaried, the immunostimulating coating of the present invention acts inthe same manner regardless of the type of surgical device to which it isapplied. The need for a coating such as that of the present inventionand the method in which it functions is generally described herein belowand with more specificity as the present invention applies to a surgicalmesh.

[0004] Surgical meshes are porous, gauze-like sheet materials which maybe woven or spun from a variety of organic and synthetic materials.Common uses of surgical meshes include the repair of herniations and useas a structural member in gynecological surgeries. The materials fromwhich surgical meshes are made must be biocompatible, chemically andphysically inert, non-carcinogenic, mechanically strong, and easilyfabricated and sterilized. Most synthetic surgical meshes are woven frommonofilament or multifilament fibers to form a mesh having pores ofvarying sizes and geometries. Other synthetic surgical meshes are formedin a node and fibril arrangement in which the mesh is comprised oflarger sections or nodes which are interconnected by fibrils of the meshmaterial. A non-exhaustive list of common surgical meshes is given inTable 1 below. TABLE 1 Chemical Component Trade Name Type Porespolypropylene Marlex (CR Bard, Cranston, RI) Mono- Irregular filamentProlene Mono- Diamond (Ethicon, Somerville, NJ) filament Atrium Mono-Irregular (Atrium Medical, Hudson, NH) filament polytetra- Teflon (CRBard, Haverill, MA) Multi- Circular fluoroethylene filament PTFEexpanded Gore-tex Multi- Node and PTFE (WL Gore, Flagstaff, AZ) filamentFibril Macropore polyethylene Mersilene Multi- Hexagonal terephthalate(Ethicon, Somervill, NJ) filament polyglycolic Dexon (absorbable) Multi-Diamond acid (Davis + Geck, filament American Cyanamid, Danbury, CT)Polyglactin 910 Vicryl (absorbable) Multi- Diamond (Ethicon, Somerville,NJ) filament

[0005] Organic surgical meshes are typically derived from human oranimal sources. Homologous surgical meshes may be derived from thetissues of a donor, from animal tissues, or from cadaveric tissues.Autologous surgical meshes are meshes that are derived from a patient'sown body, and may comprise dermagraphs, fascia tissues, and dura mater.

[0006] The most common use of surgical meshes involves the reinforcementof herniations. Surgical meshes are also used in gynecologicalprocedures including abdominal sacrocolopopexy and as suburethralslings. Other procedures which require surgical meshes includelaparosopic retropubic urethropexy, intraperitoneal placement foradhesion prevention, the repair of pelvic floor hernias, rectoceles, andcystoceles. It is to be understood that the aforementioned surgicalprocedures do not comprise a complete list of all uses of organic andsynthetic surgical meshes. New and varied uses for surgical meshes, andfor all surgical devices, are being discovered on an ongoing basis andthe present invention is to be construed to be applicable to all presentand future uses of surgical devices such as a surgical mesh.

[0007] In many surgical procedures, it is desirable that a surgical meshbecome incorporated into the tissues surrounding a surgical site. Oneexample of such a surgical procedure is the reinforcement and repair ofa herniation. In the repair of a hernia, and after the hernia has itselfbeen closed using standard surgical techniques, a surgical mesh ofappropriate size and shape is placed over the newly repaired hernia andsecured in place using sutures, staples, surgical adhesives, or anyother suitable connecting means. As the tissues surrounding the surgicalsite heal, granulation tissues growing at and around the surgical sitebegin to produce an extracellular matrix which, in a process calledfibrosis, infiltrates and attaches to the material of the surgical meshsecured over the surgical site. Incorporation of the surgical mesh intothe surgical site by the extracellular matrix strengthens the tissues atthe surgical site and helps prevent re-injury.

[0008] The rate of recovery of a patient who has undergone a surgeryutilizing a surgical mesh is strongly related to the rate at which thesurgical mesh is incorporated into the tissues surrounding the surgicalsite. The rate of incorporation of the surgical mesh as well as thepotential for infection and the potential for clinical complications isin turn related to the physical properties of the surgical mesh used.For example, synthetic meshes having pores or interstices of less than10 μm in size may theoretically promote infection in that small bacteria(less than 1 μm in size) may enter the surgical site through the mesh,while important and larger macrophages and polymorphonuclear leukocytesare prevented from passing through the mesh to the surgical site. Inaddition, the number, size, and shape of the pores play an importantrole in tissue bonding to the surgical mesh. Generally, surgical mesheshaving larger pore sizes are difficult for fibroblasts to adhere to.Furthermore, if a surgical mesh is too stiff, it may cause continuingmechanical injury to the tissues surrounding the surgical site withwhich it comes into contact. In these cases, a prolonged inflammatoryreaction may significantly increase patient recovery time and may alsocause clinical complications such as mesh extrusion and entericfistulas.

OBJECTS OF THE INVENTION

[0009] Because the ailments which require the use of surgical meshes aretypically quite serious, recovery from surgeries undertaken to alleviateor cure these ailments can be protracted. Therefore, it is desirable tofacilitate or speed up the healing and recovery process where surgicalmeshes are used.

[0010] Accordingly, it is an object of the present invention to providea coating for a surgical device such as a surgical mesh that promotesthe rapid incorporation and acceptance of the surgical device by thetissues surrounding the surgical site at which the surgical device hasbeen implanted. Another object of the present invention is to stimulatethe immune system to prevent surgical site infections. Yet anotherobject of the present invention is permit the use of synthetic surgicalmeshes and other surgical devices that are prone to rejection by or moredifficult to incorporate into the tissue surrounding a surgical site.

SUMMARY OF THE INVENTION

[0011] The present invention essentially comprises a β-D-glucancomposition that is applied to a preselected surgical device.Preferably, the β-D-glucan composition is a cereal derived β-D-glucanmade from one of oats, barley, or wheat, however other sources ofβ-D-glucan are also contemplated. Examples of other suitable sources ofβ-D-glucan include microbial sources such as yeast, bacteria, andfungus. A preferred embodiment of the present invention comprises abiocompatible surgical mesh that is typically used for reinforcing asurgical site. These surgical meshes may be synthetic or organic inorigin. Synthetic surgical meshes are commonly made from polypropylene,polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethyleneterephthalate, polyglycolic acid, polyglactin, dacron-polythenereinforced silicone and polyethylene among others. Organic surgicalmeshes may be derived from human sources, animal sources, and cadavericsources.

[0012] The present invention also comprises a method of promoting theacceptance of a surgical device into the tissues into which the surgicaldevice is implanted. This method comprises the step of applying animmunostimulating agent comprising a β-D-glucan to the surgical devicebefore implantation thereof at the surgical site.

[0013] One method of applying an imunostimulating agent such asβ-D-glucan to a biocompatible surgical device comprises the steps ofpreparing an aqueous solution of a cereal derived β-D-glucan, immersingthe pre-selected surgical device in the aqueous solution of β-D-glucan,and evaporating the water component of the aqueous solution.Alternatively, one may prepare sheets of β-D-glucan and apply thesepreformed sheets of β-D-glucan to a pre-selected surgical device. Thesheets are formed by preparing an aqueous solution comprising a cerealderived β-D-glucan and placing the aqueous solution in a drying tray toevaporate the water component of the solution. The residue left in thedrying tray is in the form of a β-D-glucan sheet. Sheets of β-D-glucanso formed are then applied to the surgical device by means of a suitableadhesive or by wetting the surgical mesh to partially dissolve the sheetof β-D-glucan.

[0014] Another method of applying a β-D-glucan to a surgical devicecomprises the steps of applying a suitable solvent to the surgicaldevice and then applying a β-D-glucan powder to the wetted surface ofthe surgical device such that the β-D-glucan powder dissolves into thesolvent to form a substantially uniform coating upon the biocompatiblesurgical device. Finally, the solvent is evaporated from thesubstantially uniform coating of β-D-glucan upon the biocompatiblesurgical device.

[0015] Another method of applying a immunostimulating coating to asurgical device involves spraying an aqueous solution of theimmunostimulating coating onto the surgical device and then evaporatingthe water component of the solution to leave a suitable coating on thesurface of the surgical device. The spraying method may also be used inan electrostatic spraying application that involves giving the aqueoussolution being sprayed and the surgical device opposing electrostaticcharges such that the aqueous solution is attracted to, and uniformlycovers, the surgical device.

[0016] Vacuum deposition may also be used to apply an immunostimulatingcoating to a surgical device. In this application method, an aqueoussolution is applied to a selected surgical device and a vacuum issubsequently drawn there around. The vacuum acts to drawn the aqueoussolution tightly to the surface of the surgical device. The watercomponent of the aqueous solution is thereafter evaporated to set thecoating upon the surgical device.

[0017] The objectives and advantages of the invention will be more fullydeveloped in the following description, made in conjunction with theaccompanying drawings and wherein like reference characters refer to thesame or similar parts throughout the several views.

DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 is an electron micrograph of a portion of an uncoatedpolypropylene surgical mesh that was implanted in a test animal for aduration of five days;

[0019]FIG. 2 is an electron micrograph of a portion of a β-D-glucancoated polypropylene surgical mesh that was implanted in a test animalfor a duration of five days;

[0020]FIG. 3 is a drawing of a generalized chemical structure of amicrobe-derived (1-3) β-D-glucan that may be used in the surgical meshcoating of the present invention;

[0021]FIG. 4 is a drawing of a generalized chemical structure of amicrobe-derived (1-3)(1-6) β-D-glucan that may be used in the surgicalmesh coating of the present invention; and

[0022]FIG. 5 is a drawing of the generalized chemical structure ofmixed-linkage cereal-derived (1-3)(1-4) β-D-glucan that may be used inthe surgical mesh coating of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0023] Although the disclosure hereof is detailed and exact to enablethose skilled in the art to practice the invention, the physicalembodiments herein disclosed merely exemplify the invention which may beembodied in other specific structure. While the preferred embodiment hasbeen described, the details may be changed without departing from theinvention, which is defined by the claims.

[0024] The present invention comprises an immunostimulating coating thatis applied to a surgical device for the purpose of speeding recoverytime of the patient. While the present invention is intended for use inhumans, veterinary applications are also contemplated. The term surgicaldevice as used herein is intended to encompass any structure or devicethat is intended for implantation at or to come into extended contactwith a surgical site in a patient's body.

[0025] In a preferred embodiment of the present invention a pre-selectedsurgical mesh material, either organic or synthetic, has applied theretoa β-D-glucan composition. As used herein, the term “applied” is intendedto embrace both coating and/or impregnation. Based on animal studies, itis anticipated that the addition of the β-D-glucan coating of thepresent invention will significantly reduce the recovery time of apatient. B-D-glucans may be derived from a number of different materialsbut in general, β-D-glucans are derived from cereal sources such asoats, barley and wheat or microbial sources such as bacteria, yeast, andfungi.

[0026] B-D-glucans, and especially cereal derived β-D-glucans, inducerapid differentiation of human monocytes into macrophages, the primarycell type associated with both wound healing and immunostimulation.While any β-D-glucan may be used to coat a surgical mesh in accordancewith the present invention, it is preferred to utilize cereal derivedβ-D-glucans to coat a chosen surgical mesh.

[0027] The stimulating effect of the β-D-glucan compound helps toprevent or to fight infection at the surgical site and will promote therapid incorporation of the surgical mesh into the tissues at thesurgical site. Furthermore, surgical meshes to which tissues do noteasily adhere, such as polytetrafluoroethylene (PTFE) and expandedpolytetrafluoroethylene (ePTFE), may, through the increased stimulationof fibrosis made possible by the use of a β-D-glucan coating, be moresuccessfully used in situations requiring the surgical mesh to becomeincorporated into the tissues surrounding the surgical site. Theaddition of a β-D-glucan composition to a surgical mesh will also allowthe use of more flexible surgical meshes which might not otherwise beconducive to tissue incorporation or adhesion in place of more rigidsurgical meshes which are more prone to causing clinical complications.

[0028] B-D-glucan coatings may also be applied to organic surgicalmeshes derived from autologous and homologous sources. A β-D-glucancoating will provide a smooth lubricated surface on a surgical meshwhich will facilitate the surgical placement of the mesh.

[0029] Compounds classified as β-D-glucans comprise a large group ofhigh molecular weight polymers containing glucopyranosyl units inbeta-linked chains. B-D-glucans are found in essentially all livingcells which are enclosed by cell walls, with considerable structuralvariation dependent on source. They are highly unbranchedhomopolysaccharides and isomerically diaposed to a α-D-glucan (e.g.starch) which is typically non-functional as a structural supportcomponent of the cell.

[0030] As depicted in FIG. 3, β-D-glucans derived from microbes havebeen generally characterized as essentially comprising (1-3)-linkedchains of glucopyranosyl units. With the recent advances in testidentification methods, yeast-derived glucans having primarily(1-3)-linkages with a relatively small number of (1-6)-linkages (FIG. 4)have been identified. Yeast-derived glucan polymers are often associatedwith mannose, and typically have a helically coiled chain shape.

[0031] The mixed linkage glucan polymers found in cereals are quitedifferent from yeast-derived and bacteria-derived polymers. Glucansderived from cereal grains such as oats, barley, and wheat, as shown inFIG. 5, have (1-3) and (1-4) linkages and generally have a linear orkinked linear chain.

[0032] Cereal-derived glucan (CDG) may be characterized as follows:

[0033] a. CDG is a long chain, unbranched polysaccharide which typicallycomprises about 3-4 percent of oat and barley grains. The CDGconcentration is greater, e.g. 7-10 percent, in the milled bran fractionof oats.

[0034] b. CDG is found in the endosperm and aleurone cell walls of mostcereal grains. The microbe-derived glucans occur in the cell wall of theyeast or bacteria.

[0035] c. CDG is a mixed-linkage molecule containing about 70 percent(1-4)-linkages and about 30 percent (1-3)-linkages. The (1-3)-linkedunits mostly occur singly whereas the (1-4)-linked units typically occurin groups of three or four glucopyranosyl units. Thus, the resultantstructure is a series of short runs of 3 or 4 (1-4)-linkedglucopyranosyl units, adjacent runs connected by (1-3) linkages. Thefrequencies of the groups of three (cellotriosyl) and four(cellotetraosyl)glucopyranosyl units also tend to be characteristic ofthe source, being affected by cereal variety, tissue age, and stage ofmaturity. Oat-derived CDG typically has more of the groups of threeconsecutive (1-4)-linked glucopyranosyl units than does barley-derivedCDG. The ratio of trisaccharide to tetrasaccharide groups is about 2:1for oats and closer to 3:1 for barley. CDG differs from microbe-derivedglucans, which have all (1-3)-linkages or mostly (1-3)-linkages withsome (1-6)-linkages.

[0036] d. CDG is a linear molecule, while yeast-derived glucan forms ahelical shape.

[0037] e. The degree of polymerization of CDG is in the range of about1200-1800. On the other hand, yeast-derived β-D-glucan has a much lowerdegree of polymerization, i.e. about 60-80. Cellulose, the primaryconstituent of plant cell walls, has all β (1-4) linkages and a degreeof polymerization of about 10,000 to 15,000.

[0038] f. CDG forms viscous solutions in warm water. On the other hand,yeast-derived glucan is insoluble in water but dispersible in aqueoussystems.

[0039] g. CDG occurs within the grain with a fairly broad range of MW,i.e. about 200,000 to 700,000. The molecular weight is believed to bedependent upon the grain species, grain source, glucan extractionconditions and particular laboratory. Microbe-derived glucan has a muchlower molecular weight, in the range of about 10,000 to 14,000.Cellulose has a molecular weight of about 700,000.

[0040] h. The use of CDG as a food component has been studiedextensively by various researchers; studies have included the use of CDGin regulation of glucose metabolism, hypoglycemic response, reduction inserum cholesterol, and the like.

[0041] Thus, in terms of chemical structure and molecular weight, CDG ismuch more like cellulose than are the microbial-derived glucans. CDG,especially that derived from oats and barley, induces rapiddifferentiation of human monocytes into macrophages, the primary celltype associated with both wound healing and immunostimulation.

[0042] It is to be noted that the term β-D-glucan incorporates bothβ-D-glucan itself and derivatives thereof. Specifically, it is oftendesirable to treat β-D-glucan, and particularly microbe derivedβ-D-glucan, so as to improve its solubility. Such treatments can alterthe molecular structure of the glucan molecules, while retaining theimmunostimulating properties of thereof. Accordingly, any glucanderivative that retains the desired immunostimulating properties of aβ-D-glucan are to be considered within the scope of the presentinvention.

[0043] Preferably a β-D-glucan coating is applied to a surgical mesh bybeing sprayed onto the surgical mesh. Alternatively, a surgical mesh maybe immersed in the β-D-glucan composition which is later dried. Othermethods for applying a β-D-glucan coating to a surgical mesh includeapplying the β-D-glucan onto a surgical mesh using a brush or rollers orbonding a preformed sheet or film of β-D-glucan to a surgical mesh. Toform a sheet or film of β-D-glucan, an aqueous solution of β-D-glucan isprepared and placed in a drying tray. β-D-glucan will, upon evaporationof the water of the aqueous solution, form a pliable sheet or film whichmay be glued to a pre-selected surgical mesh using a suitable adhesive.Alternatively, the β-D-glucan sheet or film may be adhered to apre-selected surgical mesh by first wetting the mesh and then applyingthe β-D-glucan film to the prepared mesh.

[0044] It has also been found helpful in the application of a β-D-glucancoating to a surgical mesh to apply pressure to the surgical mesh beingcoated. It is preferred to completely impregnate the surgical mesh withthe β-D-glucan composition. However, it may be desirable in certainsituations to apply β-D-glucan compositions to only a single side of asurgical mesh. It is to be understood that a β-D-glucan coating may beapplied to a surgical mesh in any manner and is not limited to theexamples set forth herein.

EXAMPLE 1

[0045] A suitable polypropylene surgical mesh was obtained from CousinsBiotech, SAS, France (BIOMESH® W1). The selected surgical mesh hadcharacteristics including a weight of 50 g/m2 and a thickness of 0.30mm.

[0046] A 0.5 weight percent β-D-glucan (oat derived) aqueous solutionwas prepared. Two 10 cm×30 cm BIOMESH® W1 surgical meshes were placed ina 10 inch×15 inch drying tray in a laminar flow hood. 250 g of aβ-D-glucan aqueous solution was poured into the trays with the preparedsurgical meshes. Each of the surgical meshes were completely immersed inthe β-D-glucan solution. The surgical meshes were then allowed to dry at20-25° C. over a period of 48 hours. The now-coated surgical meshes werethen packaged, sealed, and sterilized using commonly known procedures.

[0047] A double blind intramuscular implantation animal study was thencompleted according to USP XXIII and ISO 10993 procedures comparing theβ-D-glucan coated surgical mesh and an identical uncoated polypropylenemesh.

[0048] After five days, the coated and uncoated surgical meshes wereremoved from their intramuscular implantation sites. Macroscopicobservations of the respective surgical meshes showed dramaticdifferences between the two biopsies. The uncoated surgical mesh wasrelatively clear of ingrown fibrous tissues and was very easily removedfrom the surrounding tissue by simply pulling on the surgical mesh.Conversely, the β-D-glucan coated surgical mesh was difficult todistinguish from the surrounding tissue at the biopsy site and wasdifficult to remove. The β-D-glucan coated surgical mesh showedsubstantial integration of the surrounding tissue whereas the uncoatedmesh was still relatively unincorporated.

[0049]FIG. 1 is an electron micrograph of a portion of the uncoatedsurgical mesh after being implanted for a duration of five days. Themagnification of FIG. 1 is approximately 250×. As can be seen in FIG. 1,incorporation of the uncoated surgical mesh by an extracellular matrixhas only begun. The fibers of the uncoated polypropylene surgical meshare clearly visible. Referring next to FIG. 2 which is an electronmicrograph of a portion of the β-D-glucan coated polypropylene surgicalmesh after a duration of five days, it can be seen that considerablecolonization by fibrous tissue has taken place within the coatedsurgical mesh. In FIG. 2, the coated surgical mesh itself is not clearlyvisible and is extensively covered by a new extracellular matrix.

[0050] The benefits of rapid integration into and acceptance by thetissue at a surgical site are also very important to the success ofsurgically implantable devices and structures other than surgicalmeshes. In addition to its use as a coating for an implantable surgicalmesh as described above, β-D-glucan has proven efficacious as a coatingfor a variety of surgically implantable device and structures includingcoronary appliances such as stents, pacemakers, and leads forpacemakers; on tissue augmentation devices such as breast implants andbulking agents used in cosmetic surgery and incontinence remediationprocedures; on reconstruction materials such as nasal reconstructionmaterials and structural supports such as screws, plates, pins,artificial joints, dental implants and sutures, and on other devices andstructures of similar type.

[0051] Surgically implantable devices and structures that will benefitfrom a coating of β-D-glucan are fashioned from myriad substances, bothartificial and organic, including but not limited to polyester,polypropylene, polyethylene, polyurethane, polyolefin, polyvinylchloride, silk, elastin, keratin, cartilage, ceramics,polytetrafluoroethylene, rayon, gortex, cellulose, collagen matrix,silicone, metals such as titanium, gold, silver and the like, metallicalloys such as stainless steel and the like, carbon in the form ofgraphite, diamond and the like, and various forms of carbon or otherexotic composites.

[0052] A β-D-glucan coating may be applied to an implantable surgicaldevice in much the same manner as β-D-glucan is applied to a surgicalmesh. A necessarily incomplete listing of typical coating procedures isset forth hereinbelow.

[0053] For implantable surgical devices that are thin and porous such aswound dressings and surgical meshes, tray drying is an appropriate meansfor coating such an object with the β-D-glucan. In tray drawing, theimplantable device is submerged in a shallow tray filled with a suitableβ-D-glucan solution. A predetermined percentage of the water in theβ-D-glucan solution is then evaporated through air or oven drying,thereby leaving the surgical device coated with the β-D-glucan. Surgicaldevices such as wound dressings and surgical meshes may also be dippedinto a β-D-glucan solution. In applying a β-D-glucan solution to asurgical device in this manner, the surgical device is submersed in asolution of a β-D-glucan and subsequently dried either by air drying oroven drying. This process can be repeated to obtain a desired thicknessor uniformity of the coating on the surgical device.

[0054] Where a surgical device is not easily submerged in a β-D-glucansolution, it may be necessary to apply the β-D-glucan coating in theform of a powder. Powder application of a β-D-glucan coating begins bywetting the surgical device with water or another suitable solvent. Thepowdered β-D-glucan is then applied to the surface. As the water orother solvent evaporates, the glucan remains bound to the surface of thesurgical device.

[0055] As indicated above, a sheet of glucan may also be applieddirectly to a surgical device using water or another solvent as anadhesive whereby heat bonding or by pressing the β-D-glucan sheet intobonding contact with the surgical device. This method is especiallyuseful in applying β-D-glucan to wound dressings and to surgical meshesand to other surgical devices that may be laid flat.

[0056] Another method for applying β-D-glucan to a surgical device is tosimply use a brush or foam pad to apply a solution of β-D-glucan to thesurgical device. As can be appreciated, brush application of aβ-D-glucan coating to a surgical device is very akin to painting thesurgical device with the β-D-glucan solution.

[0057] Spraying a coating of β-D-glucan onto a surgical device isespecially useful where the surgical device has a complex surface or itis necessary to process high numbers of the surgical devices in aproduction run. In spray coating applications, the surgical devices maybe placed on a flat surface or on a vertically oriented rack and thensprayed with the β-D-glucan solution. Surgical devices supported on avertically oriented rack are typically sprayed over their entire surfacein one step. Surgical devices that are sprayed on a flat surface mayhave to be turned in order to spray the remaining surface of thesurgical device. Another means for spray coating surgical devices with aβ-D-glucan solution involves the use of a typical tablet coating machinecommonly used in the pharmaceutical industry. Once a spray coating ofβ-D-glucan has been applied to a surgical device, the β-D-glucan coatingwill be dried by air drying or oven drying.

[0058] A type of β-D-glucan application that is especially well suitedto high volume processing of surgical devices is the electrostaticapplication of the β-D-glucan to the surgical devices. In this type ofapplication, the surgical devices to be coated are placed in contactwith an electrostatically charged supporting structure such as a metaltable or a vertically oriented metal rack. A spray head for spraying theβ-D-glucan solution onto the surgical devices is electrostaticallycharged in opposition to the charge applied to the surgical devices byits supporting structure. In this way, the charged particles of theβ-D-glucan coating solution will be electrostatically attracted to thecharged surgical devices. Subsequent to coating, the β-D-glucan solutionis typically dried by air drying or oven drying.

[0059] Where it is desirable to impregnate the surface pores of asurgical device with the β-D-glucan coating, vacuum integration may bethe desired means for applying the coating. Vacuum integration of aβ-D-glucan solution into the surface of a surgical device involvessubmerging or otherwise covering the surgical device with the β-D-glucansolution and applying a vacuum around the surgical device so as to forcethe β-D-glucan solution into any pores or other irregularities in thesurface of the surgical device. Subsequent to application it ispreferable to dry the applied β-D-glucan coating by air or oven drying.

[0060] An exemplary embodiment of the present invention involves thecoating of a breast implant with a β-D-glucan solution. In coating thebreast implant, a two percent solution of β-D-glucan in the water wasfirst prepared. The breast implant was then placed in a ring-shapeddipper. The breast implant was then dipped into the β-D-glucan solutionusing the dipper, and after a predetermined amount of time removedtherefrom. Because of the nature of the breast implant, the β-D-glucansolution was then allowed to air dry under controlled conditions. Oncethe β-D-glucan solution was dry, the breast implant was removed from thedipper and packaged according to standard procedures.

[0061] Another example of the present invention involves the coating ofsurgical screws commonly used in orthopedic applications. In coating thesurgical screws, a one percent solution of β-D-glucan and water wasfirst prepared. The one percent solution of β-D-glucan was then placedin a spray container. The surgical screws were then placed on a dryingscreen and sprayed with the glucan solution, allowing the excess glucansolution to be collected below the screen. A drying screen having thenow coated surgical screws thereon was then moved to a drying area toallow the screws to air dry. Once dry, the screws were removed from thedrying screen and packaged for use.

[0062] The foregoing is considered as illustrative only of theprinciples of the invention. Furthermore, since numerous modificationsand changes will readily occur to those skilled in the art, it is notdesired to limit the invention to the exact construction and operationshown and described. While the preferred embodiment has been described,the details may be changed without exceeding the broad scope of theinvention, which is defined by the claims.

What is claimed is:
 1. A biocompatible surgical device for implantationat a surgical site having applied thereto a beta D glucan composition.2. The biocompatible surgical device for implantation at a surgical siteof claim 1 wherein the beta D glucan composition is derived from one ofoats, barley, or wheat.
 3. The biocompatible surgical device forimplantation at a surgical site of claim 1 wherein the beta D glucancomposition is derived from one of yeast, bacteria, and fungus.
 4. Abiocompatible surgical device for implantation at a surgical sitecomprising: a surgical device fabricated from a material chosen from agroup comprising polyester, polypropylene, polyethylene, polyurethane,polyolefin, polyvinyl chloride, silk, elastin, keratin, cartilage,ceramics, polytetrafluoroethylene, rayon, gortex, cellulose, collagenmatrix, silicone, titanium, gold, silver, stainless steel, graphite,diamond and carbon fiber composite materials, said surgical devicehaving applied thereto an immunostimulating agent.
 5. The biocompatiblesurgical device for implantation at a surgical site of claim 4 whereinsaid imunostimulating agent comprises a cereal derived beta D glucancomposition.
 6. The biocompatible surgical device for implantation at asurgical site of claim 4 wherein the beta D glucan composition isderived from one of yeast, bacteria, and fungus.
 7. An organicbiocompatible surgical device for implantation at a surgical site forreinforcing said surgical site having applied thereto animunostimulating agent.
 8. The organic biocompatible surgical device forimplantation at a surgical site of claim 7 wherein said organic surgicaldevice is derived from one of a human source, an animal source, and acadaveric source.
 9. The organic biocompatible surgical device forimplantation at a surgical site of claim 7 wherein said imunostimulatingagent is a cereal derived beta D glucan composition.
 10. The organicbiocompatible surgical device for implantation at a surgical site ofclaim 9 wherein said beta D glucan composition is derived from one of agroup comprising oats, barley, and wheat.
 11. The organic biocompatiblesurgical device for implantation at a surgical site of claim 7 whereinsaid imunostimulating agent is derived from one of yeast, bacteria, andfungus.
 12. A biocompatible surgical device for implantation at asurgical site comprising a device chosen from a group comprisingcoronary appliances, tissue augmentation devices, nasal reconstructionmaterials, screws, plates, pins, artificial joints, dental implants, andsutures, the surgical device having applied thereto a cereal derivedbeta D glucan composition.
 13. The biocompatible surgical device forimplantation at a surgical site of claim 12 wherein said surgical devicematrix is fashioned of a material selected from a group comprisingpolyester, polypropylene, polyethylene, polyurethane, polyolefin,polyvinyl chloride, silk, elastin, keratin, cartilage, ceramics,polytetrafluoroethylene, rayon, gortex, cellulose, collagen matrix,silicone, titanium, gold, silver, stainless steel, graphite, diamond andcarbon fiber composite materials.
 14. The biocompatible surgical devicefor implantation at a surgical site of claim 13 wherein said beta Dglucan composition is derived from one of a group comprising oats,barley, and wheat.
 15. The biocompatible surgical device forimplantation at a surgical site of claim 12 wherein said surgical deviceis derived from one of a human source, an animal source, and a cadavericsource.
 16. The biocompatible surgical device for implantation at asurgical site of claim 15 wherein said beta D glucan composition isderived from one of a group comprising oats, barley, and wheat.
 17. Amethod of applying an imunostimulating agent to a biocompatible surgicaldevice comprising the steps of: a. preparing an aqueous solutioncomprising a beta D glucan; b. immersing a pre-selected surgical devicein said aqueous solution; and c. evaporating the water component of theaqueous solution.
 18. The method of applying an imunostimulating agentto a biocompatible surgical device of claim 17 wherein said beta Dglucan is a cereal derived beta D glucan.
 19. The method of applying animunostimulating agent to a biocompatible surgical device of claim 17wherein said beta D glucan is derived from one of oats, barley andwheat.
 20. The method of applying an imunostimulating agent to abiocompatible surgical device of claim 17 wherein said beta D glucan isderived from one of yeast, bacteria, and fungus.
 21. A method ofapplying an imunostimulating agent to a biocompatible surgical devicecomprising the steps of: a. preparing an aqueous solution comprising abeta D glucan; b. placing said aqueous solution in a drying tray; c.evaporating the water component of said aqueous solution to produce asheet of beta D glucan; and d. applying said sheet of beta D glucan tosaid surgical device.
 22. The method of applying an imunostimulatingagent to a biocompatible surgical device of claim 21 further comprisingthe steps of: a. applying an adhesive to said surgical device to securesaid sheet of beta D glucan to said surgical device.
 23. The method ofapplying an imunostimulating agent to a biocompatible surgical device ofclaim 21 further comprising the steps of: a. applying water to saidsurgical device to secure said sheet of beta D glucan to said surgicaldevice.
 24. The method of applying an immunostimulating agent to abiocompatible surgical device of claim 21 wherein said beta D glucan isa cereal derived beta D glucan.
 25. The method of applying animmunostimulating agent to a biocompatible surgical device of claim 21wherein said beta D glucan is derived from one of oats, barley andwheat.
 26. The method of applying an immunostimulating agent to abiocompatible surgical device of claim 21 wherein said beta D glucan isderived from one of yeast, bacterial, and fungi.
 27. A method ofapplying an immunostimulating agent to a biocompatible surgical devicecomprising the steps of: applying a suitable solvent to thebiocompatible surgical device; applying to the wedded biocompatiblesurgical device a β-D-glucan powder such that the β-D-glucan powderdissolves into the solvent to form a substantially uniform coating uponthe biocompatible surgical device; and evaporating the solvent from thesubstantially uniform coating of β-D-glucan upon the biocompatiblesurgical device.
 28. The method of applying an immunostimulating agentto a biocompatible surgical device of claim 27 wherein said β-D-glucanis a cereal-derived β-D-glucan.
 29. The method of applying animmunostimulating agent to a biocompatible surgical device of claim 27wherein said β-D-glucan is derived from one of coats, barley, and wheat.30. A method of applying an immunostimulating agent to a biocompatiblesurgical device comprising the steps of: preparing an aqueous solutioncomprising a β-D-glucan; placing the aqueous solution of β-D-glucan in aspraying mechanism; coating a predetermined portion of the surface ofthe biocompatible surgical device with the aqueous β-D-glucan solutionby spraying the aqueous solution onto the surface of the biocompatiblesurgical device; and drying the aqueous solution of β-D-glucan depositedon the surface of the biocompatible surgical device.
 31. The method ofapplying an immunostimulating agent to a biocompatible surgical deviceof claim 30 wherein said β-D-glucan is a cereal-derived β-D-glucan. 32.The method of applying an immunostimulating agent to a biocompatiblesurgical device of claim 30 wherein said β-D-glucan is derived from oneof oats, barley, and wheat.
 33. A method of applying animmunostimulating agent to a biocompatible surgical device comprisingthe steps of: preparing an aqueous solution comprising a β-D-glucan;placing said aqueous solution in an electrostatically charged sprayingdevice; placing the biocompatible surgical device upon a supportstructure having an electrostatic charge opposite that of the sprayingdevice; spraying the electrostatically charged aqueous solution onto theoppositely charged biocompatible surgical device so as to form a coatingthereon; and, drying the aqueous solution on the surface of thebiocompatible surgical device.
 34. The method of applying animmunostimulating agent to a biocompatible surgical device of claim 33wherein said β-D-glucan is a cereal-derived β-D-glucan.
 35. The methodof applying an immunostimulating agent to a biocompatible surgicaldevice of claim 34 wherein said β-D-glucan is derived from one of oats,barley, and wheat.
 36. A method of applying an immunostimulating agentto a biocompatible surgical device comprising the steps of: applying anaqueous solution comprising β-D-glucan to the surface of a biocompatiblesurgical device; drawing a vacuum around the coated biocompatiblesurgical device; removing the biocompatible surgical device from thevacuum; and, drying the aqueous solution on the surface of thebiocompatible surgical device.
 37. The method of applying animmunostimulating agent to a biocompatible surgical device of claim 36wherein said β-D-glucan is a cereal-derived β-D-glucan.
 38. The methodof applying an immunostimulating agent to a biocompatible surgicaldevice of claim 37 wherein said β-D-glucan is derived from one of oats,barley, and wheat.
 39. A method of promoting the acceptance of asurgical device into the tissues into which the surgical device isimplanted, the method comprising the step of applying animmunostimulating agent to the surgical device before implantation. 40.A method of promoting the acceptance of a surgical device into thetissues into which the surgical device is implanted, the methodcomprising the step of applying an immunostimulating agent comprising aβ-D-glucan to the surgical device before implantation.
 41. A method ofpromoting the acceptance of a surgical device into the tissues intowhich the surgical device is implanted, the method comprising the stepof applying an immunostimulating agent comprising a cereal-derivedβ-D-glucan to the surgical device before implantation.
 42. A method ofpromoting the acceptance of a surgical device into the tissues intowhich the surgical device is implanted, the method comprising the stepof applying an immunostimulating agent to the surgical device beforeimplantation at a surgical site, the immunostimulating agent comprisinga β-D-glucan derived from one of a group comprising yeast, fungi, cerealgrains, and bacteria.
 43. The organic biocompatible surgical device forimplantation at a surgical site of claim 15 wherein saidimmunostimulating agent is derived from one of yeast, bacteria, andfungus.
 44. The method of applying an immunostimulating agent to abiocompatible surgical device of claim 36 wherein said β-D-glucan isderived from one of yeast, bacteria, and fungus.